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Significant main effects of treatment group (prior to BenjaminiHochberg correction since none were significant after correction, although the necessity of correction for multiple comparisons in exploratory analyses remains unresolved 49 ) were observed for the unclassified group and ten classified genera, namely, Acetatifactor , Akkermansia , Erysipelatoclostridium , [ Eubacterium ] coprostanoligenes group , Family XIII UCG-001 , Lactobacillus , Parasutterella , Ruminiclostridium 6 , Ruminococcaceae UCG-004 , and Ruminococcaceae UCG-009

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MECHANISM CATEGORIES RESEARCH CONDITIONS SAFETY Side effects Limited human safety data Animal studies report wide therapeutic window Known interactions Methyl-donor depletion theoretical with chronic dosing (NNMT methylates nicotinamide using SAM) Contraindications Pregnancy/lactation (unstudied) REGULATORY STATUS FDA Not FDA-approved

Data were expressed as permeability ( P app ) calculated using the following formula: Efflux Ratio (R e ) was calculated using the formula: 2.4